Acid-sensing ion channels (ASICs) are proton-gated voltage-independent ion channels located on neurons in the peripheral and central nervous systems. ASICs are also found in non-neuronal cells like muscle cells, synoviocytes, and bone cells. ASICs belong to the epithelial sodium channel/degenerin (ENaC/DEG) family of amiloride-sensitive transmembrane ion channel proteins (see(37, 41, 78)). Four genes within mammalian genomes encode seven subunits to date—ASIC1a, ASIC1b, ASIC1b2, ASIC2a, ASIC2b, ASIC3 and ASIC4.(1, 15, 26, 27, 40, 54, 69, 73) Homomeric and heteromeric ASIC subunits combine to form trimeric ASICs,(13, 34) which depending on the subunit composition in the DRG display differences in pH sensitivity, current kinetics and ion selectivity.(11, 20, 29, 53) ASICs respond to acidosis, play a significant role in nociceptive processing of hyperalgesia both peripherally and centrally.(1, 3, 6, 8-10, 15, 16, 21, 27, 28, 37, 40-42, 54, 65, 66, 68, 70, 72-74, 76) 
Illness or trauma can often lead to decreases in pH which activate ASICs. The tissue acidosis associated with inflammation, infection, and ischemia causes pain (Reeh, P. W., and Steen, K. H. (1996). Tissue acidosis in nociception and pain. Prog Brain Res 113, 143-151). Acidosis also generates proton-dependent transient and sustained Na.30 currents in cultured sensory neurons (Bevan, S., and Yeats, J. (1991). Protons activate a cation conductance in a sub-population of rat dorsal root ganglion neurons. J Physiol (Lond) 433, 145-161; Davies, N. W., Lux, H. D., and Morad, M. (1988). Site and mechanism of activation of proton-induced sodium current in chick dorsal root ganglion neurons. J Physiol (Lond) 400, 159-187).
Pain is a common ailment. For example, pain such as musculoskeletal pain affects the great majority of the population, and nearly half of the population suffers from chronic musculoskeletal pain. Currently available treatments are inadequate to treat most chronic pain conditions. Therefore, for these and other reasons there is a need for a safe treatment of pain that could be safe and used in long-term modalities.